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Medicine Oct 2019As a fabulous part of Oriental Medcine, acupuncture and moxibustion possesses the advantage of high safety, convenience and less adverse effects. Unruptured follicular...
BACKGROUND
As a fabulous part of Oriental Medcine, acupuncture and moxibustion possesses the advantage of high safety, convenience and less adverse effects. Unruptured follicular luteinization syndrome is a common cause of infertility in women of reproductive age, which seriously affects the physical and mental health of patients. Certain studies have reported that acupuncture can improve the rate of pregnancy in women with unruptured follicular luteinization syndrome. In this protocol, the effects of acupuncture on rates of ovulation and pregnancy among women with unruptured follicular luteinization syndrome will be further explored.
METHODS
Electronic bibliographic databases such as: MEDLINE, EMBASE, PsycINFO, Global Health, The Cochrane Library (Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials (CENTRAL), Cochrane Methodology Register), Health Technology Assessment Database, and Web of Science (Science and Social Science Citation Index), PubMed, Chinese Biomedical Databaseare, Chinese VIP Information, Chinese National Knowledge Infrastructure (CNKI), all helpful to identify relevant randomized controlled trials (RCTs) of effects of acupuncture on rates of ovulation and pregnancy among women with unruptured follicular luteinization syndrome. The pooled odds ratio of achieving a clinical pregnancy, ongoing pregnancy, or live birth were used as the main outcome and the secondary outcome includes the changes of ovarian artery dynamics before and after treatment, so as to the adverse reactions of treatment. We will use RevMan 5.3 software to help us to analyze all data and use the Cochrane evaluation manual 5.1.0 to help us to assess the methodological quality for incorporated RCTs.
RESULT
This systematic review will provide evidence for assessing the effects of acupuncture on rates of ovulation and pregnancy in women with unruptured follicular luteinization syndrome.
CONCLUSION
The results of this study will be a useful reference for clinical treatment with acupuncture to improve rates of ovulation and pregnancy among women with unruptured follicular luteinization syndrome.
Topics: Acupuncture Therapy; Female; Humans; Infertility, Female; Luteinization; Meta-Analysis as Topic; Ovarian Follicle; Ovulation; Pregnancy; Pregnancy Rate; Syndrome; Systematic Reviews as Topic
PubMed: 31626086
DOI: 10.1097/MD.0000000000017294 -
Journal of Ovarian Research Apr 2017Ovarian epithelial tumor (OET) is a silent disease of late diagnosis and poor prognosis. Currently treatment options are limited and patient response to treatment is...
BACKGROUND
Ovarian epithelial tumor (OET) is a silent disease of late diagnosis and poor prognosis. Currently treatment options are limited and patient response to treatment is difficult to predict so there is a serious need to delineate the real pathogenesis to predict tumour prognosis. Prohibitin (PHB) is an evolutionarily protein that regulates the cell cycle. TGF-β has been shown to be a positive and negative regulator of cellular proliferation and differentiation. The present study provides an overview on the role played by PHB1, TGF-β and LH in ovarian cancer.
METHODS
The study was conducted on 60 patients with ovarian tumors (benign, borderline and malignant) and 20 healthy volunteers. LH and TGF-β serum levels were measured by ELISA. Expression of prohibitin and LHR-mRNA were assessed by IHC and TaqMan® real time gene expression assay, respectively.
RESULTS
Serum levels of LH and TGF-β were significantly decreased among borderline and malignant groups. There was significant over-expression of LHRmRNA in malignant group. Prohibitin expression was significantly increased in malignant ovarian tissue. Strong negative correlations were found between LHR mRNA expression and serum LH levels, and between IHC score of prohibitin and serum levels of LH among patients with borderline ovarian tumors.
CONCLUSION
Steady decline of LH and TGF-B serum levels, from benign cystadenoma to borderline tumor to carcinoma, suggests their inhibitory role against OET cell growth. Increased PHB1 expression in OET suggests its proliferative activity that can be regulated by luteinisation and/or TGF-β. Furthermore increased LHR mRNA tissue expression can provide hope for using LH in treatment of some types of ovarian cancers.
Topics: Adult; Cystadenocarcinoma, Papillary; Cystadenocarcinoma, Serous; Cystadenoma, Mucinous; Cystadenoma, Papillary; Female; Gene Expression Regulation, Neoplastic; Humans; Luteinization; Luteinizing Hormone; Middle Aged; Neoplasm Proteins; Ovarian Neoplasms; Ovary; Prohibitins; RNA, Messenger; RNA, Neoplasm; Receptors, LH; Repressor Proteins; Transforming Growth Factor beta
PubMed: 28427435
DOI: 10.1186/s13048-017-0325-4 -
Reproductive Biology and Endocrinology... Oct 2014Gonadotropins extracted from the urine of post-menopausal women have traditionally been used to stimulate folliculogenesis in the treatment of infertility and in... (Comparative Study)
Comparative Study Review
Gonadotropins extracted from the urine of post-menopausal women have traditionally been used to stimulate folliculogenesis in the treatment of infertility and in assisted reproductive technology (ART). Products, such as human menopausal gonadotropin (hMG), consist not only of a mixture of the hormones, follicle-stimulating hormone (FSH), luteinising hormone (LH) and human chorionic gonadotropin (hCG), but also other biologically active contaminants, such as growth factors, binding proteins and prion proteins. The actual amount of molecular LH in hMG preparations varies considerably due to the purification process, thus hCG, mimicking LH action, is added to standardise the product. However, unlike LH, hCG plays a different role during the natural human menstrual cycle. It is secreted by the embryo and placenta, and its main role is to support implantation and pregnancy. More recently, recombinant gonadotropins (r-hFSH and r-hLH) have become available for ART therapies. Recombinant LH contains only LH molecules. In the field of reproduction there has been controversy in recent years over whether r-hLH or hCG should be used for ART. This review examines the existing evidence for molecular and functional differences between LH and hCG and assesses the clinical implications of hCG-supplemented urinary therapy compared with recombinant therapies used for ART.
Topics: Animals; Chorionic Gonadotropin; Drug Contamination; Drug Industry; Evidence-Based Medicine; Female; Fertility Agents, Female; Humans; Infertility, Female; Luteinizing Hormone; Recombinant Proteins; Reproductive Techniques, Assisted
PubMed: 25280580
DOI: 10.1186/1477-7827-12-95 -
The Journal of Reproduction and... Aug 2023Progesterone (P4) and cortisol production increase in luteinized granulosa cells (LGCs) during the periovulatory period, but their interaction is not well established....
Progesterone (P4) and cortisol production increase in luteinized granulosa cells (LGCs) during the periovulatory period, but their interaction is not well established. Therefore, we investigated their interaction in cultured bovine LGCs. Granulosa cells were collected from follicles of 2-5 mm in diameter and cultured in DMEM/F-12 supplemented with 10% fetal calf serum for up to 14 days. P4 production and the expression of steroidogenic acute regulatory protein (STAR), cholesterol side-chain cleavage enzyme (CYP11A1), and 3β-hydroxysteroid dehydrogenase type 1 (HSD3B1) rapidly increased until day 10 and remained high thereafter. No de novo production of cortisol from P4 was detected during the culture period. The expression of 11β-hydroxysteroid dehydrogenase type 1 (HSD11B1), which converts cortisone to cortisol, increased dramatically on day two, decreased until day 8, and remained relatively constant. To investigate how P4 and cortisol influence each other's production, LGCs were treated with trilostane (a P4 synthesis inhibitor), nomegestrol acetate (NA, a synthetic progestogen), P4, and/or cortisol for 24 h on days 6 and 12 of culture. Trilostane suppressed P4 and STAR expression while elevating HSD11B1 and HSD3B1 expression and cortisol production. Concomitant treatment with NA or P4 dose-dependently decreased cortisol production and HSD11B1 and HSD3B1 expression but elevated STAR expression in both days 6 and 12. Conversely, cortisol treatment increased HSD11B1 and HSD3B1 expression and decreased STAR expression without influencing P4 production. These results indicate that progestogens suppress cortisol production by modulating HSD11B1 expression and that progestogens and cortisol differentially regulate STAR, HSD3B1, and HSD11B1 expression in bovine LGCs.
Topics: Female; Animals; Cattle; Progesterone; Hydrocortisone; Progestins; Granulosa Cells; Cholesterol Side-Chain Cleavage Enzyme; Multienzyme Complexes; Cells, Cultured
PubMed: 37344443
DOI: 10.1262/jrd.2023-005 -
Neuroendocrinology 2014The KNDy neuropeptides, kisspeptin, neurokinin B (NKB) and dynorphin A (Dyn), have been implicated in regulating pulsatile luteinising hormone (LH) secretion. Studies of... (Review)
Review
The KNDy neuropeptides, kisspeptin, neurokinin B (NKB) and dynorphin A (Dyn), have been implicated in regulating pulsatile luteinising hormone (LH) secretion. Studies of the interactions between KNDy signalling systems, however, are currently few. Although the stimulatory effect of kisspeptin and the inhibitory effect of Dyn on the gonadotropin-releasing hormone pulse generator are widely accepted, the effects of NKB in rodents are variable and sometimes controversial. Literature describing increased LH secretion in response to NKB receptor agonism predominates and is in line with human physiology, as well as the pathophysiology of pubertal failure associated with disruption of NKB signalling. However, the robust suppression of the LH pulse, induced by the same treatment under hypoestrogenic conditions, may hold clues as to the mechanisms of reproductive inhibition under pathological conditions. This review discusses the recent evidence for this paradox and outlines a revised working model incorporating the mechanisms by which KNDy neuropeptides modulate the reproductive axis.
Topics: Animals; Arcuate Nucleus of Hypothalamus; Dynorphins; Gonadotropin-Releasing Hormone; Humans; Hypothalamo-Hypophyseal System; Kisspeptins; Luteinizing Hormone; Male; Mice; Neuroendocrinology; Neurokinin B; Pituitary-Adrenal System; Rats; Reproduction; Signal Transduction
PubMed: 24356581
DOI: 10.1159/000357734 -
Journal of Neuroendocrinology Jan 2020The central nervous system regulates fertility via the release of gonadotrophin-releasing hormone (GnRH). This control revolves around the hypothalamic-pituitary-gonadal... (Review)
Review
The central nervous system regulates fertility via the release of gonadotrophin-releasing hormone (GnRH). This control revolves around the hypothalamic-pituitary-gonadal axis, which operates under traditional homeostatic feedback by sex steroids from the gonads in males and most of the time in females. An exception is the late follicular phase in females, when homeostatic feedback is suspended and a positive-feedback response to oestradiol initiates the preovulatory surges of GnRH and luteinising hormone. Here, we briefly review the history of how mechanisms underlying central control of ovulation by circulating steroids have been studied, discuss the relative merit of different model systems and integrate some of the more recent findings in this area into an overall picture of how this phenomenon occurs.
Topics: Animals; Estradiol; Feedback, Physiological; Gonadotropin-Releasing Hormone; Gonads; Humans; Hypothalamo-Hypophyseal System; Hypothalamus; Luteinizing Hormone; Neurosecretory Systems; Pituitary Gland
PubMed: 31054210
DOI: 10.1111/jne.12724 -
Cell Communication and Signaling : CCS May 2022The LH surge is a pivotal event that triggers multiple key ovarian processes including oocyte maturation, cumulus expansion, follicular wall rupture and luteinization of...
BACKGROUND
The LH surge is a pivotal event that triggers multiple key ovarian processes including oocyte maturation, cumulus expansion, follicular wall rupture and luteinization of mural granulosa and theca cells. Recently, LH-dependent activation of the Hippo signaling pathway has been shown to be required for the differentiation of granulosa cells into luteal cells. Still, the precise interactions between Hippo and LH signaling in murine granulosa cells remain to be elucidated.
METHODS
To detect the expression of effectors of the Hippo pathway, western blot, immunohistochemical and RT-qPCR analyses were performed on granulosa cells treated with LH in vitro or isolated from immature mice treated with eCG and hCG. Cultured granulosa cells were pretreated with pharmacologic inhibitors to identify the signaling pathways involved in Hippo regulation by LH. To study the roles of Yap1 and Taz in the regulation of the LH signaling cascade, RT-qPCR and microarray analyses were done on granulosa cells from Yap1;Taz mice treated with an adenovirus to drive cre expression. RT-qPCR was performed to evaluate YAP1 binding to the Areg promoter following chromatin immunoprecipitation of granulosa cells collected from mice prior to or 60 min following hCG treatment.
RESULTS
Granulosa cells showed a transient increase in LATS1, YAP1 and TAZ phosphorylation levels in response to the ovulatory signal. This Hippo activation by LH was mediated by protein kinase A. Furthermore, Yap1 and Taz are required for the induction of several LH target genes such as Areg, Pgr and Ptgs2, and for the activation of the ERK1/2 pathway. Consistent with these results, there was a substantial overlap between genes that are upregulated by LH and those that are downregulated following loss of Yap1/Taz, highlighting a major role for Hippo in mediating LH actions in the ovulation process. Finally, we showed that there is a marked recruitment of YAP1 to the Areg promoter of granulosa cells in response to hCG stimulation.
CONCLUSIONS
Overall, these results indicate that Hippo collaborates with the cAMP/PKA and ERK1/2 pathways to participate in the precise regulation of the LH cascade, and that Areg, as a direct transcriptional target of YAP1, is involved in mediating its actions in the ovary. Video Abstract.
Topics: Amphiregulin; Animals; Female; Granulosa Cells; Luteinizing Hormone; Mice; Phosphorylation; Signal Transduction
PubMed: 35619099
DOI: 10.1186/s12964-022-00843-1 -
The Cochrane Database of Systematic... Nov 2015Gonadotrophin-releasing hormone agonists (GnRHa) are commonly used in assisted reproduction technology (ART) cycles to prevent a luteinising hormone surge during... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Gonadotrophin-releasing hormone agonists (GnRHa) are commonly used in assisted reproduction technology (ART) cycles to prevent a luteinising hormone surge during controlled ovarian hyperstimulation (COH) prior to planned oocyte retrieval, thus optimising the chances of live birth.
OBJECTIVES
To evaluate the effectiveness of the different GnRHa protocols as adjuncts to COH in women undergoing ART cycles.
SEARCH METHODS
We searched the following databases from inception to April 2015: the Cochrane Menstrual Disorders and Subfertility Group Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL) in the Cochrane Library (2015, Issue 3), MEDLINE, EMBASE, CINAHL, PsycINFO, and registries of ongoing trials. Reference lists of relevant articles were also searched.
SELECTION CRITERIA
We included randomised controlled trials (RCTs) comparing any two protocols of GnRHa used in in vitro fertilisation (IVF) or intracytoplasmic sperm injection (ICSI) cycles in subfertile women.
DATA COLLECTION AND ANALYSIS
Two review authors independently selected studies, assessed trial eligibility and risk of bias, and extracted the data. The primary outcome measure was number of live births or ongoing pregnancies per woman/couple randomised. Secondary outcome measures were number of clinical pregnancies, number of oocytes retrieved, dose of gonadotrophins used, adverse effects (pregnancy losses, ovarian hyperstimulation, cycle cancellation, and premature luteinising hormone (LH) surges), and cost and acceptability of the regimens. We combined data to calculate odds ratios (OR) for dichotomous variables and mean differences (MD) for continuous variables, with 95% confidence intervals (CIs). We assessed statistical heterogeneity using the I² statistic. We assessed the overall quality of the evidence for the main comparisons using 'Grading of Recommendations Assessment, Development and Evaluation' (GRADE) methods.
MAIN RESULTS
We included 37 RCTs (3872 women), one ongoing trial, and one trial awaiting classification. These trials made nine different comparisons between protocols. Twenty of the RCTs compared long protocols and short protocols. Only 19/37 RCTs reported live birth or ongoing pregnancy.There was no conclusive evidence of a difference between a long protocol and a short protocol in live birth and ongoing pregnancy rates (OR 1.30, 95% CI 0.94 to 1.81; 12 RCTs, n = 976 women, I² = 15%, low quality evidence). Our findings suggest that in a population in which 14% of women achieve live birth or ongoing pregnancy using a short protocol, between 13% and 23% will achieve live birth or ongoing pregnancy using a long protocol. There was evidence of an increase in clinical pregnancy rates (OR 1.50, 95% CI 1.18 to 1.92; 20 RCTs, n = 1643 women, I² = 27%, moderate quality evidence) associated with the use of a long protocol.There was no evidence of a difference between the groups in terms of live birth and ongoing pregnancy rates when the following GnRHa protocols were compared: long versus ultrashort protocol (OR 1.78, 95% CI 0.72 to 4.36; one RCT, n = 150 women, low quality evidence), long luteal versus long follicular phase protocol (OR 1.89, 95% CI 0.87 to 4.10; one RCT, n = 223 women, low quality evidence), when GnRHa was stopped versus when it was continued (OR 0.75, 95% CI 0.42 to 1.33; three RCTs, n = 290 women, I² = 0%, low quality evidence), when the dose of GnRHa was reduced versus when the same dose was continued (OR 1.02, 95% CI 0.68 to 1.52; four RCTs, n = 407 women, I² = 0%, low quality evidence), when GnRHa was discontinued versus continued after human chorionic gonadotrophin (HCG) administration in the long protocol (OR 0.89, 95% CI 0.49 to 1.64; one RCT, n = 181 women, low quality evidence), and when administration of GnRHa lasted for two versus three weeks before stimulation (OR 1.14, 95% CI 0.49 to 2.68; one RCT, n = 85 women, low quality evidence). Our primary outcomes were not reported for any other comparisons.Regarding adverse events, there were insufficient data to enable us to reach any conclusions except about the cycle cancellation rate. There was no conclusive evidence of a difference in cycle cancellation rate (OR 0.95, 95% CI 0.59 to 1.55; 11 RCTs, n = 1026 women, I² = 42%, low quality evidence) when a long protocol was compared with a short protocol. This suggests that in a population in which 9% of women would have their cycles cancelled using a short protocol, between 5.5% and 14% will have cancelled cycles when using a long protocol.The quality of the evidence ranged from moderate to low. The main limitations in the evidence were failure to report live birth or ongoing pregnancy, poor reporting of methods in the primary studies, and imprecise findings due to lack of data. Only 10 of the 37 included studies were conducted within the last 10 years.
AUTHORS' CONCLUSIONS
When long GnRHa protocols and short GnRHa protocols were compared, we found no conclusive evidence of a difference in live birth and ongoing pregnancy rates, but there was moderate quality evidence of higher clinical pregnancy rates in the long protocol group. None of the other analyses showed any evidence of a difference in birth or pregnancy outcomes between the protocols compared. There was insufficient evidence to make any conclusions regarding adverse effects.
Topics: Buserelin; Clinical Protocols; Drug Administration Schedule; Female; Fertility Agents, Female; Gonadotropin-Releasing Hormone; Humans; Leuprolide; Live Birth; Luteinizing Hormone; Ovulation Induction; Pituitary Gland; Pregnancy; Pregnancy Rate; Randomized Controlled Trials as Topic; Reproductive Techniques, Assisted; Triptorelin Pamoate
PubMed: 26558801
DOI: 10.1002/14651858.CD006919.pub4 -
Frontiers in Cell and Developmental... 2020During the luteinization after ovulation in mammalian ovary, the containing cells undergo an energy consuming function re-determination process to differentiate into...
During the luteinization after ovulation in mammalian ovary, the containing cells undergo an energy consuming function re-determination process to differentiate into luteal cells under avascular environment. Previous evidences have delineated the contribution of autophagy to the cell differentiation and the catabolic homeostasis in various types of mammalian cells, whereas few interest had been focused on the involvement of autophagy in the luteinization of granulosa cells during the formation of early corpus luteum. Herein, the present study investigated that expression and contribution of autophagy during granulosa cell luteinization and early luteal development through and experiments. The results clearly demonstrated that HIF-1α/BNIP3-mediated autophagy plays a vital role in the luteinization of granulosa cells during the early luteal formation and . In the neonatal corpus luteum, HIF-1α up-regulated BNIP3 expressions, which contributed to the autophagic initiation by disrupting beclin1 from Bcl-2/beclin1 complex and protected cells from apoptosis by curbing the skew of mitochondria balance under avascular niche. Notably, Inhibition of HIF-1α activity by echinomycin enhanced the levels of cytoplasmic cytochrome c and cell apoptosis in the nascent corpus luteum. These findings revealed that HIF-1α/BNIP3-mediated autophagy enabled the process of granulosa cell luteinization and protected the granulosa-lutein cells from further apoptosis under hypoxia niche. To our knowledge, the present study firstly clarified that HIF-1α/BNIP3-mediated autophagy contributes to the luteinization of granulosa cells during the formation of pregnant corpus luteum, which will help us further understanding the luteal biology and provide us new clues for the treatment of luteal insufficiency.
PubMed: 33537309
DOI: 10.3389/fcell.2020.619924 -
Scientific Reports Jun 2020Core Binding Factors (CBFs) are a small group of heterodimeric transcription factor complexes composed of DNA binding proteins, RUNXs, and a non-DNA binding protein,...
Core Binding Factors (CBFs) are a small group of heterodimeric transcription factor complexes composed of DNA binding proteins, RUNXs, and a non-DNA binding protein, CBFB. The LH surge increases the expression of Runx1 and Runx2 in ovulatory follicles, while Cbfb is constitutively expressed. To investigate the physiological significance of CBFs, we generated a conditional mutant mouse model in which granulosa cell expression of Runx2 and Cbfb was deleted by the Esr2Cre. Female Cbfb;Esr2;Runx2 mice were infertile; follicles developed to the preovulatory follicle stage but failed to ovulate. RNA-seq analysis of mutant mouse ovaries collected at 11 h post-hCG unveiled numerous CBFs-downstream genes that are associated with inflammation, matrix remodeling, wnt signaling, and steroid metabolism. Mutant mice also failed to develop corpora lutea, as evident by the lack of luteal marker gene expression, marked reduction of vascularization, and excessive apoptotic staining in unruptured poorly luteinized follicles, consistent with dramatic reduction of progesterone by 24 h after hCG administration. The present study provides in vivo evidence that CBFs act as essential transcriptional regulators of both ovulation and luteinization by regulating the expression of key genes that are involved in inflammation, matrix remodeling, cell differentiation, vascularization, and steroid metabolisms in mice.
Topics: Animals; Core Binding Factor Alpha 1 Subunit; Core Binding Factor beta Subunit; Female; Fertility; Granulosa Cells; Infertility, Female; Luteinization; Mice; Mice, Knockout; Ovulation; Reproduction
PubMed: 32555437
DOI: 10.1038/s41598-020-64257-0